CA2610740A1

CA2610740A1 - Nebuliser

Info

Publication number: CA2610740A1
Application number: CA002610740A
Authority: CA
Inventors: Matthias Hausmann; Uwe Hegemann
Original assignee: Individual
Current assignee: Boehringer Ingelheim International GmbH
Priority date: 2005-06-24
Filing date: 2006-06-23
Publication date: 2006-12-28
Also published as: US7950388B2; JP2008543684A; CA2608296C; ECSP078028A; EP1893344A1; BRPI0613138A2; ZA200708563B; EP1893343A1; MX2007015403A; RU2008101804A; US8479725B2; JP5249752B2; US20070029475A1; IL186594A0; AR055977A1; CN101189071A; JP2008543466A; WO2006136426A1; EP1893344B1; CA2608296A1

Abstract

A nebuliser (1) for a fluid (2) with a conveying tube (9) for conveying fluid (2) and a method of producing a thick-walled capillary are proposed. The conveying tube (9) or the capillary is of multiparty and/or double-walled construction, and in particular is made up of a number of parts such as an inner tube (23) and an outer tube (24) . This allows the device to be manufactured more easily and cheaply, in particular when the inner diameters are very small.

Description

Nebuliser The present invention relates to a nebuliser according to the preamble of claim 1 and a method of producing a thick-walled capillary.

A nebuliser available under the trade name "Respimat" in the form of an inhaler is known, as illustrated in its basic principle in WO 91/14468 Al and in a specific configuration in WO 97/12687 Al (Figs. 6a, 6b) as well as in Figs. 1 and 2 of the accompanying drawings. The nebuliser has a conveyor device with a conveying tube for conveying and atomiiing the fluid. The conveying tube is constructed, in particular, as a thick-walled massive capillary, as shown in Fig. 3b of WO 97/12687 Al. The conveying tube is therefore very difficult and complex to produce.

Capillaries with a small internal diameter and thin walls are generally obtainable. Capillaries with a thick wall and small manufacturing tolerances are however, very difficult to produce and often have undesirably rough inner walls. This can be explained by the many forming steps (which are often, in the last analysis, carried out without a core because of the small internal diameter), needed to produce a thick-walled massive capillary.

In the present invention the term "capillary" relates in particular to microfluidic, preferably elongate structures with a hydrauiic diameter of less than 1000 m, particularly preferably less than 500 m. The internal cross-section is preferably but not necessarily at least essentially round. The same is true in particular of the outer contour of the preferably tubular or cylindrical capillary. However, the capillary may also have other non-round internal and/or external cross-sections or contours.

The term "thick-walled" refers according to the invention to a capillary particularly when the mean inner diameter is less than 50% of the outer diameter, particularly less than 30 %, and/or when the wall thickness is more than 0.3 mm, preferably more than 0.5 mm.

i The aim of the present invention is to provide a nebuliser having a conveying tube and a method of producing a capillary, wherein the conveying tube or the capillary is simple and inexpensive to produce with a thick-walled construction and particularly with a smooth inner wall, while having great stability.

This aim is achieved by a nebuliser according to claim I or a method according to claim 35. Advantageous further features are recited in the subsidiary claims.

In one aspect the present invention comprises making a thick-walled capillary or a conveying tube of a nebuliser preferably formed therefrom with a double-walled construction. This enables the object to be produced more easily and hence more cheaply than in the prior art, with low manufacturing tolerances.

In particular, it is possible to achieve a smoother inner surface. The double-walled construction, in fact, makes it possible to use standard commercial thin-walled capillaries, so that the large number of form ! ing steps that were previously required can be eliminated or reduced.

Particularly preferably, an inner tube is concentrically installed in an outer tube, in particular, to form the conveying tube or the thick-walled capillary.
The tubes are then constructed in particular as thin-walled capillaries which can be obtained cheaply and to a high quality.

The proposed thick-walled capillary is preferably used as i conveying tube in a proposed nebuliser. The following discussion will therefore be directed primarily to the use of the capillary as a conveying element or conveying tube for a fluid which is to be nebulised in a nebuliser of this kind. However, the thick-walled capillary may also be used for other purposes. This also applies to the method described for producing the conveying tube or the thick-walled capillary.

Further advantages, features, properties and aspects of the present invention will become apparent from the claims and the following description of preferred embodiments with reference to the drawings, wherein:

Fig. 1 is a schematic section through a known nebuliser in the non-tensioned state;
Fig. 2 is a schematic section through the known nebuliser in the tensioned state, rotated through 90 compared with Fig. 1;

Fig. 3 is a schematic section, not to scale, through a proposed nebuliser with a conveying tube according to a first embodiment;

Fig. 4 is a schematic section through a conveying tube according to a second embodiment;

Fig. 5 is a magnification of a detail of Fig. 4;

Fig. 6 is another magnification of a detail of Fig. 4;
Fig. 7 is a further magnification of a detail from Fig. 4;

Fig. 8 is a schematic section, not to scale, through a conveying tube according to a third embodiment;

Fig. 9 is a magnification of a detail from Fig. 8;
Fig. 10 is another magnification of a detail from Fig. 8;
Fig. 11 is a further magnification of a detail from Fig. 18;

Fig. 12 is a schematic section, not to scale, through a conveying tube according to a fourth embodiment;

Fig. 13 is magnification of a detail from Fig. 12;

Fig. 14 is another magnification of a detail from Fig. 12;

Fig. 15 is a schematic section, not to scale, througli a conveying tube according to a fifth embodiment;

Fig. 16 is a magnification of a detail from Fig. 15;

Fig. 17 is a schematic section, not to scale, through a conveying tube according to a sixth embodiment;

Fig. 18 is a magnification of a detail from Fig. 17; and Fig. 19 is a schematic section, not to scale, through a conveying tube according to a seventh embodiment.

In the Figures, the same reference numerals have been used for identical or similar parts, resulting in corresponding or comparable properties and advantages, even if the associated description is not repeated.

Figs. 1 and 2 show a known nebuliser 1 for atomising a fluid 2, particularly a highly effective pharmaceutical composition or the like, diagrammatically shown in the non-tensioned state (Fig. 1) and in the tensioned state (Fig. 2).
The nebuliser I is constructed in particular as a portable inlialer and preferably operates without propellant gas.
When the fluid 2, preferably a liquid, more particularly a pharmaceutical composition, is nebulised, an aerosol is formed, which can be breathed in or inhaled by a user (not shown). Usually the inhaling is done at least once a day, more particularly several times a day, preferably at set intervals, depending on the complaint from which the patient is suffering.

The known nebuliser 1 has an insertable and preferably exchangeable container 3 which holds the fluid 2. The container thus forms a reservoir for the fluid 2 which is to be nebulised. Preferably, the container 3 contains an amount of fluid 2 or active substance which is sufficient to provide up to 200 dosage units, for example, i.e. to allow up to 200 sprays or applications.

The container 3 is substantially cylindrical or cartridge-shaped and once the nebuliser 1 has been opened the container can be inserted therein from below and changed if desired. It is of rigid construction, the fluid 2 preferably being held in a fluid chamber 4 in the form of a collapsible bag in the container 3.
The nebuliser 1 also has a conveying device, particularly a pressure generator 5 for conveying and nebulising the fluid 2, particularly in a preset and optionally adjustable dosage amount.

The nebuliser 1 or pressure generator 5 has a holder 6 for the container 3, an associated drive spring 7, only partly shown, with a locking element 8 which can be manually operated to release it, a conveying tube 9 preferably in the form of a thick-walled capillary, with an optional valve, particularly a non-return valve 10, a pressure chamber 11 and/or an expulsion nozzle 12 in the region of a mouthpiece 13. The container 3 is fixed in theinebuliser 1 via the holder 6, particularly by locking engagement, such that the conveying tube 9 penetrates into the container 3. The holder 6 may be constructed so that -the container 3 can be detached and exchanged.

As the drive spring 7 is axially tensioned the holder 6 with the container 3 and the conveying tube 9 is moved downwards in the drawings and fluid 2 is sucked out of the container 3 through the non-return valve 10 into the pressure chamber 11 of the pressure generator 5.

During the subsequent relaxation after actuation of the locking element 8 the fluid 2 in the pressure chamber 11 is put under pressure as the conveying tube 9 with its now closed non-return valve 10 is moved back upwards by the relaxation of the drive spring 7 and now acts as a pressing' ram. This pressure forces the fluid 2 through the expulsion nozzle 12, whereupon it is nebulised into an aerosol 14, as shown in Fig. 1.

A user or patient (not shown) can inhale the aerosol 14, while an air supply can be sucked into the mouthpiece 13 through at least one air supply opening 15.

The nebuliser 1 comprises an upper housing part 16 and an inner part 17 which is rotatable relative thereto (Fig. 2) having an upper part 17a and a lower part 17b (Fig. 1), while an in particular manually op'erable housing part 18 is releasably fixed, particularly fitted onto the inner part 17, preferably by means of a retaining element 19. In order to insert and/or replace the container 3 the housing part 18 can be detached from the nebuliser 1.

The housing part 18 can be rotated relative to the upper housing part 16, carrying with it the part 17b of the inner part 17 which is lower down in the drawings. As a result the drive spring 7 is tensioned in the axial direction by means of a gear (not shown) acting on the holder 6. During tensioning the container 3 is moved axially downwards until the container 3 assumes an end position as shown in Fig. 2. In this state the drive spring 7 is under tension.
When the tensioning is carried out for the first time, an axially acting spring disposed in the housing part 18 comes to abut on the base of the container and by means of a piercing element 21 pierces the contain'er 3 or a seal at the bottom when it first comes into abutment therewith, for venting. During the 15 nebulising process the container 3 is moved back into its original position shown in Fig. 1 by the drive spring 7, while the conveying tube 9 is moved with its outlet end 22 into the pressure chamber 11. The !container 3 and the conveying element or conveying tube 9 thus execute a lifting movement during the tensioning process or for drawing up the fluid and during the 20 atomising process.

The construction and mode of operation of several embodiments of a proposed nebuliser 1 and method will now be described in more detail, referring to the other Figures, which are not to scale, but emphasising only the essential differences from the nebuliser 1 according to 'Figs. 1 and 2. The remarks relating to Figs. 1 and 2 thus apply accordingly or in a supplementary capacity, while any desired combinations of features of the nebuliser 1 according to Figs. 1 and 2 and the nebuliser 1 according;to the embodiments described below or with one another are possible.

-g-Fig. 3 shows in schematic section the container 3 and part of the associated proposed nebuliser 1 according to a first embodiment. The conveying tube 9 comprises an inner tube 23 and an outer tube 24, which are preferably arranged concentrically to one another and/or formed as thin walled, in particular standard commercial capillaries.

The conveying tube 9 is thus double walled and preferably multi-part in construction and especially is in the form of a thick walled but preferably not massive capillary. The double walled and particularly multi-part construction makes it possible in particular to manufacture the conveying tube 9 particularly cheaply and/or precisely, most preferably with a smooth and/or round inner wall or contour.

The inner tube 23 forms a conveying channel 25 on the inside. The annular space 26 between the inner tube 23 and the outer tube 24 preferably forms a venting channel in the first embodiment. Alternatively, the annular chamber 26 may also preferably be sealed off in gas tight manner.

The two tubes 23 and 24 are preferably firmly joined together by welding, e.g.
in the region of their ends. However, the two tubes 23 and 24 may also be joined together by some other method, for example by adhesive bonding, soldering, deformation or the like.

The multi-part construction of the conveying tube 9 - either from the two tubes 23 and 24, as explained above, or from even more parts - may if necessary also be used independently of any venting, in particular in a nebuliser 1 of the type described hereinbefore or some other nebuliser 1. In particular, the venting channel in the conveying tube 9 may be omitted or, as already mentioned, sealed off.

In the first embodiment the conveying tube 9 is preferably, fixedly attached to the holder 6. In particular, the conveying tube 9 or its outer tube 24 is provided for this purpose with a retaining region 27 - preferably having a corrugated outer contour or the like. The conveying tube 9 is preferably injection moulded with the holder 6 at the retaining regioh 27. The holder 6 thus preferably engages by interlocking engagement in the retaining region 27 or thereon. Thus the conveying tube 9 is axially secured in the holder 6 by interlocking engagement.

The conveying tube 9 or the thick walled capillary preferably has an at least substantially smooth or cylindrical outer wall which is optionally only interrupted by the retaining region 27 which is relatively 'short in relation to the overall length, in particular.

In the first embodiment an immersion tube 28, in particular, adjoins the conveying tube 9 and extends preferably to the base inside the container 3. In the embodiment shown the immersion tube 28 is connected to a closure 30 of the container 3, in particular via a retaining portion 29 which widens out in a funnel shape, so that the conveying tube 9 on insertion into the container 3 or when the closure 30 is pierced, can be inserted into the position shown in the retaining portion 29 of the immersion tube 28 and a fluidic connection is established between the conveying channel 25 and the immersion tube 28.
However, the immersion tube 28 is only optional. As an alternative, this may also be omitted. The conveying tube 9 then extends preferably up to or into the region of the bottom of the container 3 or fluid chamber 4.

The conveying tube 9 is used in particular as a piston for pumping the fluid 2 in the nebuliser 1 or in the conveying device or pressure generator 5. The conveying tube 9 should have a relatively large outer diameter. By contrast, the inner diameter of the conveying tube 9 - i.e. the inner diameter of the inner tube 23 or the diameter of the conveying channel 25 thus formed -should be relatively small in order to achieve a small dead volume.
Accordingly, it is necessary or at least desirable for the conveying tube 9 to be fairly thick-walled - particularly in the sense described hereinbefore, and in the first embodiment this is achieved by concentrically arranging the inner tube 23 inside the outer tube 24. In order to achieve the desired pumping action and/or ensure defined volumes or avoid dead spaces, the annular space 26 between the inner tube 23 and outer tube 24 is preferably closed off at least at the delivery end, particularly in fluid tight manner and most particularly preferably in gas tight manner as well.

The conveying tube 9 preferably comprises the valve, particularly the non return valve 10, which in the embodiment shown is disposed at the downstream end of the conveying tube 9 or at the end which extends into the pressure chamber 11.

The conveying tube 9 or the thick-walled capillary preferably consists at least essentially or totally of metal, particularly stainless steel, most preferably austenitic chrome nickel steel. Preferably at least the inner tube 23 and the outer tube 24 consist of the same material, particularly metal or stainless steel, as mentioned previously.

The conveying tube 9 or the thick-walled capillary preferably has an outer diameter (of the outer tube 24) of 1- 2 mm and/or an inner diameter (of the inner tube 23) of 0.1 - 0.6 mm. Preferably the outer diameter is at least twice or three times as great as the inner diameter. The wall thicknesses of the tubes 23, 24 are preferably about 0.1 mm or less.

The conveying tube 9 or the thick-walled capillary preferably has a wall thickness (radial spacing of the inner wall of the inner tube 23 from the outer wall of the outer tube 24) of at least 0.3 mm, most prefera i ly around 0.5 mm or more.

The proposed thick-walled or double-walled construction~ of the conveying tube 9 goes beyond the preferred high displacement during its use as a piston and independently thereof leads to a particularly high stability of the conveying tube 9, which is necessary for example in ordei to allow safe and definite piercing or other type of opening of the conta ner 3 or the like.
However, this stability may also be advantageous in other ulses.

Further embodiments of the nebuliser 1 or conveying tu,be 9 or the thick-walled capillary and the preferred production of the conveying tube 9 or the thick-walled capillary are described hereinafter with ref erence to the other figures, while only essential difference from the first embodiment are particularly explained. The previous embodiments therefore apply in a corresponding or supplementary capacity.

Fig. 4 shows a second embodiment of the conveying tube 9 in section. As in the first embodiment the conveying tube 9 is preferably made in two parts, namely the inner tube 23 and the outer tube 24. Preferably the two tubes 23, 24 are welded together. The annular space 26 between the tubes 23, 24 is preferably closed off at both ends, particularly in gas tight manner.

Fig. 5 shows, in a magnified detail from Fig. 4, the valve or outlet end 22 of the conveying tube 9. The valve, particularly a non-return valve 10, is preferably formed on or by the conveying tube 9 or integrated therein, as in the first embodiment. In the second embodiment the outerl tube 24 - as in the first embodiment - preferably forms a valve region 31 extending axially beyond the end of the inner tube 23, in particular, in which a valve member 32 of the valve 10 is accommodated. The valve member 32 is preferably axially movable. The preferably inwardly crimped or otherwise deformed end 22 of the outer tube 24 or some other retaining means form an, axial stop for the valve member 32 in the outer tube 24 or valve region 31 and delimit the axial mobility of the valve member 32 accordingly.

The conveying tube 9 also preferably forms a valve seat 33 for the valve 10 for the valve body 32. The valve body 32 preferably sits axially on the valve seat 33 when the valve 10 is closed, i.e. during the nebulising process.

In the second embodiment the valve seat 33 is preferably formed by a concentric region or section of the outer tube 24, particularly an encircling narrowing or bead 34. However, other constructive solutions are also possible.
The inner tube 23 preferably has a radially widening, particularly at least partially conical connecting portion 35 which in this case is formed at the end of the inner tube 23 and expands in particular at least substantially to the inner diameter of the outer tube 24. The two tubes 23, 24 are jointed together by the connecting portion 35, particularly by welding, gluing or the like. For example, it is possible to carry out welding through the outer wall of the outer tube 24 in a substantially radial direction.

The inner tube 23 thus extends at least substantially as far as the valve seat or up to the preferably radial narrowing or bead 34, thus minimising the volume through which the fluid 2 can flow in the conveying tube 9 or conveying channe125.

Fig. 6 shows, in a magnified detail from Fig. 4, the other end of the conveying tube 9. Here again, the inner tube 23 is preferably connected to the outer tube 24 via a connecting portion 35 which widens out radially, in particular. In the embodiment shown the inner tube 23 or its connecting portion 35 preferably terminates flush with the axial end of the outer tube 24 and is axially welded to the outer tube 24 in this region, in particular.

In the second embodiment the inner tube 23 is preferably attached, particularly by welding, to the outer tube 24 at its two ends. The inner tube may, however, also be radially connected to the outer tube 24 by spacers or other means between its two ends or may be at least radially held or guided.

In the second embodiment the annular space 26 (axial interstice between the inner tube 23 and the outer tube 24) is preferably hermetically sealed, particularly in fluid tight and gas tight manner.

In the second embodiment the annular space 26 is preferably of hollow construction, i.e. it is not filled with a medium. However this is theoretically possible. For example, the interstice 26 may be at least partly filled with an adhesive, an insulating material or some other suitable material.

In the second embodiment the conveying tube 9 or outer, tube 24 preferably has an outer diameter that remains at least substantially constant over its entire length. If required, the outer diameter of the valve region 10 may also be reduced. The retaining region 27 may optionally project radially relative to the above mentioned outer diameter, as explained below.

Fig. 7 shows, in a magnified detail from Fig. 4, the retaining region 27 of the conveying tube 9. The retaining region 27 is formed in the second embodiment by an external radial projection 36, particularly in the form of a flange-like crimped edge. The projection 36 or crimped edge projects radially outwards relative to the outer diameter of the conveying tube 9 or outer tube 24. The retaining region 27 preferably serves to secure the conveying tube 9 in the holder 6 by interlocking engagement in the axial direction (see Fig. 3).
Fig. 8 shows a third embodiment of the conveying tube, 9 in section. The fourth embodiment is very similar to the second embodiment and consequently only the major differences will be described b elow.

The conveying tube 9 is preferably once again made in only two parts, namely the inner tube 23 and the outer tube 24.

Fig. 9 shows in a magnified detail from Fig. 8 the inflow end of the conveying tube 9. The inner tube 23 is preferably set back, with its connecting portion 35, relative to the end of the outer tube 24. This makes it'easier to adhere to the length tolerance of the conveying tube 9.

Fig. 10 shows in a magnified detail from Fig. 8 the valve end 22 of the conveying tube 9 (without terminal crimping and without a valve member 32).
The valve seat 33 is formed here by the axially expanding connecting portion 35 of the inner tube 23 at this end. Accordingly, in this embodiment the outer tube 24 preferably does not have any narrowing or bead 34 in this area.

Fig. 11 shows in a magnified detail from Fig. 8 the retaining region 27 of the conveying tube 9. Instead of a projection the retaining region 27 in this fourth embodiment preferably has a radial indentation or recess 37 particularly an annual groove, a step, a bead or the like, several of which may be provided one behind the other and in particular a corrugated outer contour may be formed by the retaining region 27.

According to a particularly preferred aspect the outer tube 24 at the retaining region 27 is deformed axially inwards such that it bears on the inner tube 23.

If necessary the outer tube 24 in this contact region may also be fixedly connected to the inner tube 23, e.g. by welding or adhesive bonding. This can contribute to the overall stability of the conveying tube 9.

However, it is also possible for a radial spacing to be maintained between the outer tube 24 and the inner tube 23 at the retaining region 27.

Fig. 12 shows a fourth embodiment of the conveying tube 9 shown in section.
The fourth embodiment is very similar to the second and third embodiments.
In particular, the conveying tube 9 according to the fourth embodiment is again made in only two parts, preferably the inner tube 23 and outer tube 24.
Fig. 13 shows in a magnified detail from Fig. 12_ the inflow end of the conveying tube 9. The inner tube 23 or its connecting portion 35 in the fourth embodiment has a cylindrical portion 38 which adjoins the conical or radially expanding portion of the connecting portion 35 and has an outer diameter which corresponds at least substantially to the inner diameter of the outer tube 24. The inner tube 23 is preferably connected in fluid tight and more preferably gas tight manner to the outer tube 23 via the cylindrical portion 38, e.g. by welding, gluing, or the like.

The cylindrical portion 38 or the inner tube 23 is also preferably recessed inwardly or set back relative to the associated end of the outer tube 24 in the fourth embodiment as well.

Fig. 14 shows in a magnified detail from Fig. 12 the outflow or valve end 22 i of the conveying tube 9 (without terminal crimping and without a valve member 32). In the fourth embodiment the inner tube 23 preferably forms the valve region 31 of the valve 10. In particular, the preferably at least substantially hollow cylindrical valve region 31 is directly adjacent to the conical connecting portion 35 of the inner tube 23 which forms the valve seat 33.

Preferably the receiving region 31 has an outer diameter which corresponds to the outer diameter of the outer tube 24. In this case !the outer tube 24 preferably terminates at the connecting portion 35 of the inner tube 23 and does not extend as far as the valve end of the conveying tube 9, as shown in Fig. 14. If necessary the outer tube 24 may taper conically in its end region to make it easier to connect it to the inner tube 23, e.g. by welding.
Fig. 15 shows a fifth embodiment of the conveying tube 9 in section. The fifth embodiment corresponds substantially to the fourth embodiment. The only difference is that at the inflow end the inner tube 23 is pr eferably connected via a separate spacer element 39 to the outer tube 24, as indicated in Fig.
19, which shows a magnified detail from Fig. 18. The spacer element 39 is preferably at least substantially hollow cylindrical or sleeve-shaped or annular in construction and closes off the annular space 26 axially or at its end face. In particular, the radially widening connecting portion 35 on the inner tube 23 at the inflow end can be omitted. The two tubes 23 and 24 preferably terminate together with the spacer element 39 in an end plane or axial plane and are preferably axially welded thereto. However, the spacer element 39 may also be pressed in or on, attached by gluing or by some other method.

The spacer element 39 preferably has a wall thickness of at least substantially 50 % of the difference between the inner diameter 24 and the outer diameter of the inner tube 23. The spacer element 39 is located in particular in a snug fit or press fit.

The spacer element 39 preferably has a length of less than 20 %, particularly preferably less than 10 %, of the total length of the conveying tube 9.

WO 2006/136427 ~ PCT/EP2006/006047 I
Alternatively the spacer element 39 may also extend ol er a substantially greater length, in particular to increase the kink resistance of the conveying tube 9. For example, the spacer element 39 may even extend as far as the retaining region 28 or to the indentation or bead 34.
In the fifth embodiment the conveying tube 9 is no longerI made in two parts but preferably in three parts. In spite of the greaterl number of parts manufacture is simpler as the individual components can be manufactured very simply, inexpensively and with great precision.

Fig. 17 shows a sixth embodiment of the conveying tube 9 in section. The seventh embodiment is very similar to the fifth embodiment. Instead of two parts, however, the conveying tube 9 here is made up of three parts. The retaining region 27 here is preferably in the form of an encircling annular groove or depression.

Fig. 18 shows, in a magnified detail from Fig. 17, the valve end 22 of the conveying tube 9. The conveying tube 9 in the sixth embodiment preferably has a valve member or connecting member 40 which is produced separately from the inner tube 23 and outer tube 24, and which forms the receiving region 31 of the valve 10 and/or connects the two tubes 23, 24.

The valve member or connecting member 40 has in particular a preferably conical connecting portion 35 adjoining the receiving region 31, which connects the two tubes 23, 24 and/or again forms the valve seat 33.

The outer tube 24 and the receiving region 31 of the~ valve member or connecting member 40 preferably in turn have at least substantially the same outer diameter as in the third and fourth embodiments. The outer tube 24 preferably terminates at the connecting portion 35 of the valve member or connecting member 40, as indicated in Fig. 21, where the outer tube 24 is tightly joined to the connecting member 27, in particulI ar by welding. If necessary the end part of the outer tube 24 may in turn be conically tapered.

With a correspondingly reduced diameter, a preferably at least substantially hollow cylindrical or sleeve-shaped connecting regio i 41 adjoins the connecting portion 35 and is pushed or fitted or pressed onto the inner tube and attached thereto, particularly by welding.

In particular, the valve member or connecting member 40 is constructed as a deep-drawn part which is relatively easy to produce.

Fig. 19 shows a seventh particularly preferred embodimerit of the conveying tube 9 in section. The conveying tube 9 here is preferably made up of at least four parts, namely the inner tube 23, the outer tube 24, the~ spacer element and the valve member or connecting member 40.

At the inflow end, the two tubes 23 and 24 are preferably connected by means of the spacer element 39, in particular as in the sixth embodiment.

At the outlet or valve end 22 the two tubes 23 and 24 are preferably joined together by the valve member or connecting member 40 as in the seventh embodiment.

In spite of the multiplicity of parts, namely at least fo ir components, the seventh embodiment is relatively simple and cheap to produce, particularly with low manufacturing tolerances and if necessary with !a very smooth and even inner wall..

Initially the valve member or connecting member 40 and the inner tube 23 are joined together, particularly by welding. It is particularly preferable for the welding to be carried out radially from outside in the connecting region 41.
In this way a first assembly is formed.

In addition, the outer tube 24 and the spacer element 39 are joined together, particularly by welding, to form a second assembly. The welding is preferably carried out at the end face or at the inlet end.

Then the two assemblies are combined and firmly joined together. In particular, the outer tube 24 is welded to the valve member or connecting member 40. This may be done essentially radially. Moreover, the spacer element 39 is fixedly connected to the inner tube 23, in particular axially welded thereto.

If the conveying tube 9 is provided with the optional valve 10, as in the embodiment shown, the valve member 32 (not shown) is then introduced into the valve region 10 and secured, preferably by final deforniation of the end of the conveying tube 9 or of the valve member or connecting member 40, particularly crimped inwardly, so as to form an axial abutment for the valve member 32.

In the finished conveying tube 9 the annular space 26 is preferably evacuated and/or sealed in gastight manner. If necessary the annulari space 26 may also be filled with a filler material, plastics or the like (not shown).

The valve member or connecting member 40 or the connecting portion 35 preferably has a length of less than 20 %, in particular less than 10 %, of the total length of the conveying tube 9. This makes production easier. The length -of the conveying tube 9 or outer tube 24 is preferably at least 50 mm or 50 times the inner diameter.

The preferred multi-part construction of the conveying tube 9, consisting in particular of more than two parts, preferably three or four parts, may if necessary be implemented independently of the preferred double-walled construction of the conveying tube 9. The valve 10 is most preferably formed by the valve member or connecting member 40 which is separately produced but still fixedly connected to the conveying tube 9, and which forms in particular the receiving or valve region 31 for the valve member 32 of the valve 10.

Generally, it should be pointed out that in the proposed nebuliser 1 the container 3 can preferably be inserted, i.e. incorporated in the nebuliser 1.
Consequently, the container 3 is preferably a separate component. However, the container 3 or fluid chamber 4 may theoretically be formed directly by the nebuliser 1 or part of the nebuliser 1 or may otherwise be integrated in or attached to the nebuliser 1.

As already mentioned, individual features, aspects and / or principles of the embodiments described may also be combined with one another as desired and may be used particularly in the known nebuliser according to Figs. 1 and 2 but also in similar or different nebulisers.

Unlike freestanding equipment or the like the proposed nebuliser 1 is preferably designed to be portable and in particular is a mobile hand-operated device.

The proposed solution may, however, be used not only in the nebulisers 1 specifically described here but also in other nebulisers or inhalers, e.g.
powder inhalers or so-called metered dose inhalers.

The nebuliser 1 is particularly preferably constructed as an inhaler, particularly for medicinal aerosol treatment. Alternatively, however, the nebuliser 1 may also be constructed for other purposes, preferably for nebulising a cosmetic liquid and in particular as a perfume atomiser. The container 3 accordingly contains, for example, a pharmaceutical formulation or a cosmetic liquid such as perfume or the like. Further, the proposed capillary can also be used in any kind of any dispensing device for the preferably medical fluid 2. Thus, the term "nebuliser" is to be understood preferably in such a broad sense.

1s Preferably, the fluid 2 is a liquid, as already mentioned, especially an aqueous or ethanol pharmaceutical formulation. However, it may also be some other pharmaceutical formulation, a suspension or the like, or particles or powder.
Preferred ingredients and / or formulations of the preferably medicinal fluid are listed hereinafter. As already stated, these may be aqueous or non-aqueous solutions, mixtures, formulations containing ethanol or solvent-free formulations or the like. It is particularly preferable for the fluid 2 to contain:
As pharmaceutically active substances, substance formul.ations or substance mixtures, all invaluable compounds are used such as, for example, invaluable macromolecules as disclosed in EP 1 003 478. Preferably, substances, substance formulations or substance mixtures for treating respiratory complaints and administered by inhalation are used.

Particularly preferred pharmaceutical compositions in this context are those which are selected from among the anticholinergics, betamimetics, steroids, phosphodiesterase IV inhibitors, LTD4 antagonists and EGFR kinase inhibitors, antiallergics, derivatives of ergot alkaloids; triptans, CGRP

antagonists, phosphodiesterase V inhibitors, and combinations of such active substances, e.g. betamimetics plus anticholinergics or betamimetics plus antiallergics. In the case of combinations, preferably at least one of the active substances comprises chemically bound water. Preferably, anticholinergic-containing active substances are used, as monopreparations or in the form of combined preparations.

The following are specifically mentioned as examples of the active ingredients or the salts thereof:

1s Anticholinergics which may be used are preferably selected from among tiotropium bromide, oxitropium bromide, flutropium bromide, ipratropium bromide, glycopyrronium salts, trospium chloride, tolterodine, tropenol 2,2-diphenylpropionate methobromide, scopine 2,2-diphenylpropionate methobromide, scopine 2-fluoro-2,2-diphenylacetate methobromide, tropenol 2-fluoro-2,2-diphenylacetate methobromide, tropenol 3,3',4,4'-tetrafluorobenzilate methobromide, scopine 3,3',4,4'-tetrafluorobenzilate methobromide, tropenol 4,4'-difluorobenzilate methobromide, scopine 4,4'-difluorobenzilate methobromide, tropenol 3,3'-difluorobenzilate methobromide, scopine 3,3'-difluorobenzilate methobromide, tropenol 9-hydroxy-fluorene-9-carboxylate methobromide, tropenol 9-fluoro-fluorene-9-carboxylate methobromide, scopine 9-hydroxy-fluorene-9-carboxylate methobromide, scopine 9-fluoro-fluorene-9-carboxylate methobromide, tropenol 9-methyl-fluorene-9-carboxylate methobromide, scopine 9-methyl-fluorene-9-carboxylate methobromide, cyclopropyltropin6benzilate methobromide, cyclopropyltropine 2,2-diphenylpropionate methobromide, cyclopropyltropine 9-hydroxy-xanthene-9-carboxylate methobromide, cyclopropyltropine 9-methyl-fluorene-9-carboxylate methobromide, cyclopropyltropine 9-methyl-xanthene-9-carboxylate methobromide, cyclopropyltropine 9-hydroxy-fluorene-9-carboxylate methobromide, cyclopropyltropine methy14,4'-difluorobenzilate methobrornide, tropenol 9-hydroxy-xanthene-9-carboxylate methobromide, scopine 9-hydroxy-xanthene-9-carboxylate methobromide, tropenol 9-methyl-xanthene-9-carboxylate methobromide, scopine 9-methyl-xanthene-9-carboxylate methobromide, tropenol 9-ethyl-xanthene-9-carboxy late methobromide, tropenol 9-difluoromethyl-xanthene-9-carboxylate methobromide and scopine 9-hydroxymethyl-xanthene-9-carboxylate methobromide, optionally in the form of the racemates, enantiomers or diastereomers thereof and optionally in the form of the solvates and/or hydrates thereof.

Betamimetics which may be used are preferably selected from among albuterol, bambuterol, bitolterol, broxaterol, carbuterol, clenbuterol, fenoterol, formoterol, hexoprenaline, ibuterol, indacaterol, isoetharine, isoprenaline, levosalbutamol, mabuterol, meluadrine, metaproterenol, orciprenaline, pirbuterol, procaterol, reproterol, rimiterol, ritodrine, salmeterol, salmefamol, soterenot, sulphonterol, tiaramide, terbutaline, tolubuterol, CHF-1035, HOKU-8 1, KUL- 1248, 3-(4-{6-[2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino]-hexyloxy}-butyl)-benzolsulphonamide, 5-[2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one, 4-hydroxy-7-[2- {[2- { [3-(2-phenylethoxy)propyl]sulphonyl}ethyl]-23 amino}ethyl]-2(3H)-benzothiazolone, 1-(2-fluoro-4-hydroxyphenyl)-2-[4-(1-benzimidazolyl)-2-methyl-2-butylamino]ethanol, 1-[3-(4-methoxybenzyl-amino)-4-hydroxyphenyl]-2-[4-(1-benzimidazolyl)-2-methyl-2-butylamino]ethanol, 1-[2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl]-2-[3-(4-N,N-dimethylaminophenyl)-2-methyl-2-propylamino]ethanol, 1-[2H-5-hydroxy-3-oxo-4H-1.4-benzoxazin-8-yl]-2-[3-(4-rnethoxyphenyl)-2-methyl-2-WO 2006/136427 ~ -24 PCT/EP2006/006047 -propylamino]ethanol, 1-[2H-5-hydroxy-3-oxo-4H-1.4-benzoxazin-8-yl]-2-[3-(4-n-butyloxyphenyl)-2-methyl-2-propylamino]ethanol, 1-[2H-5-hydroxy-3-oxo-4H-1.4-benzoxazin-8-yl]-2- { 4- [3-(4-methoxyphenyl)-1i.2.4-triazol-3-yl]-2-methyl-2-butylamino}ethanol, 5-hydroxy-8-(1-hydroxy-2-isopropylaminobutyl)-2H-1.4-benzoxazin-3-(4H)-one, 1-(4-amino-3-chloro-5-trifluormethylphenyl)-2-tert.-butylamino)ethanol and 1-(4-ethoxycarbonyl-amino-3-cyano-5-fluorophenyl)-2-(tert.-butylamino)ethanol, optionally in the form of the racemates, enantiomers or .diastereomers thereoI f and optionally in the form of the pharmacologically acceptable acid addition salts, solvates and/or hydrates thereof.

Steroids which may be used are preferably selected from among prednisolone, prednisone, butixocortpropionate, RPR-106541, flunisolide, beclomethasone, triamcinolone, budesonide, fluticasone, mometasone, ciclesonide, rofleponide, ST-126, dexamethasone, (S)-fluoromethyl 6a,9a-difluoro-,l7a-[(2-furanylcarbonyl)oxy]-11(3-hydroxy-l6a-methyl-3-oxo-androsta-1,4-diene-17(3-carbothionate, (S)-(2-oxo-tetrahydro-furan-3 S-yl) 6a,9a-difluoro-11(3-hydroxy-l6a-methyl-3-oxo-l7a-propionyloxy-androsta-1,4-diene-17(3-carbothionate and etiprednol-dichloroacetate (BNP-166), optionally in the form of the racemates, enantiomers or diastereomers thereof and optionally in the form of the salts and derivatives thereof, the solvates and/or hydrates thereof.

PDE IV-inhibitors which may be used are preferably selected from among enprofyllin, theophyllin, roflumilast, ariflo (cilomilast), CP-325,366, BY343, D-4396 (Sch-351591), AWD-12-281 (GW-842470), N-(3,5-dichloro-l-oxo-pyridin-4-yl)-4-difluoromethoxy-3-cyclopropylmethoxybenzamide, NCS-613, pumafentine, (-)p-[(4aR*,IObS*)-9-ethoxy-1,2,3,4,4a,10b-hexahydro-8-methoxy-2-methylbenzo[s] [ 1,6]naphthyridin-6-yl]-N,N-i diisopropylbenzamide, (R)-(+)-1-(4-bromobenzyl)-4-[(3-cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidone, 3-(cyclopentyloxy-4-methoxyphenyl)-1-(4-N'-[N-2-cyano-S-methyl-isothioureido]benzyl)-2-pyrrolidone, cis[4-cyano-4-(3-cyclopentyloxy-4-methoxyphenyl)cyclohexane-l-carboxylic acid], 2-carbomethoxy-4-cyano-4-(3-cyclopropylmethoxy-4- , difluoromethoxyphenyl)cyclohexan-l-one, cis[4-cyano-4-(3-cyclopropyl-methoxy-4-difluoromethoxyphenyl)cyclohexan-l-ol], (R)-(+)-ethyl[4-(3-cyclopentyloxy-4-methoxyphenyl)pyrrolidin-2-ylidene]acetate, (S)-(-)-ethyl [4-(3-cyclopentyloxy-4-methoxyphenyl)pyrrolidin-2-ylidene]acetate, CDP840, Bay-198004, D-4418, PD-168787, T-440, T-2585, arofyllin, atizoram, V-11294A, Cl-1018, CDC-801, CDC-3052, D-22888, YM-58997, Z-15370, 9-cyclopentyl-5,6-dihydro-7-ethyl-3-(2-thienyl)-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-a]pyridine and 9-cyclopentyl-5,6-dihydro-7-ethyl-3-(tert-butyl)-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-a]pyridin, optionally in the form of the racemates, enantiomers or diastereomers thereof and' optionally in the form of the.pharmacologically acceptable acid addition salts, solvates and/or hydrates thereof.

LTD4-antagonists which may be used are preferably selected from among ,, montelukast, 1-(((R)-(3-(2-(6,7-difluoro-2-quinolinyl)ethenyl)phenyl)-3 -(2-(2-hydroxy-2-propyl)phenyl)thio)methylcyclopropane-acetic acid, 1-(((1(R)-3(3-(2-(2,3 -dichlorothieno[3,2-b]pyridin-5-yl)-(E)-ethenyl)pheinyl)-3-(2-(1-hydroxy-1-methylethyl)phenyl)propyl)thio)methyl)cyclopropane-acetic acid, pranlukast, zafirlukast, [2-[[2-(4-tert-butyl-2-thiazolyl)-5- i benzofuranyl]oxymethyl]phenyl]acetic acid, MCC-847 (ZD-3523), MN-001, i MEN-91507 (LM-1507), VUF-5078, VUF-K-8707 and L-733321, optionally in the form of the racemates, enantiomers or diastereomers thereof, optionally in the form of the pharmacologically acceptable acid addition salts thereof and optionally in the form of the salts and derivatives thereof, the solvates and/or hydrates thereof. i EGFR-kinase inhibitors which may be used are preferably selected from among cetuximab, trastuzumab, ABX-EGF, Mab ICR-62, 4-[(3-chloro-4-fluorophenyl)amino]-6-{ [4-(morpholin-4-yl)-1-oxo-2-buten'-1-yl]amino}-7-cyclopropylmethoxy-quinazoline, 4- [(R)-(1-phenyl-ethyl)amino]-6- { [4-(morpholin-4-yl)-1-oxo-2-buten-l-yl] amino) -7-cyclopentyloxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6- { [4-((R)-6-methyl-2-oxo-morpholin-4-yl)-1-oxo-2-buten-l-yl]amino}-7-[(S)-(tetrahydrofuran-3-yl)oxy]-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[2-((S)-6-methyl-2-oxo-morpholin-4-i o yl)-ethoxy]-7-methoxy-quinazoline, 4-[(3-chloro-4-fluorophenyl)amino]-6-( {4-[N-(2-methoxy-ethyl)-N-methyl-amino]-1-oxo-2-buten, 1-yl } amino)-7-cyclopropylmethoxy-quinazoline, 4-[(R)-(1-phenyl-ethyl)amino]-6-({4-[N-(tetrahydropyran-4-yl)-N-methyl-amino]-1-oxo-2-buten-1-yl}amino)-7-cyclopropylmethoxy-quinazoline, 4-[(3-chloro-4-fluorophenyl)amino]-6-({4-[N-(2-methoxy-ethyl)-N-methyl-amino]-1-oxo-2-buten-l-yl } amino)-7-cyclopentyloxy-quinazoline, 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-buten-l-yl]amino} -7- [(R)-(tetrahydrofuran-2-yl)methoxy]-quinazoline, 4-[(3-ethynyl-phenyl)amino]-6,7~-bis-(2-methoxy-ethoxy)-quinazoline, 4-[(R)-(1-phenyl-ethyl)amino]-6-(4-hydroxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidine, 3-cyano-4-[(3-chloro-4-fluorophenyl)amino]-6-{ [4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl]amino}-7-ethoxy-quinoline, 4-[(R)-(1-phenyl-ethyl)amino]-6- { [4-((R)-6-methyl-2-oxo-morpholin-4-yl)-1-oxo-2-buten-l-yl]amino}-7-methoxy-quinazoline, 4-[(3-chloro-4-fluorophenyl)amino]-6- { [4-(morpholin-4-yl)-1-oxo-2-buten-1-yl] amino }-7-[(tetrahydrofuran-2-yl)methoxy]-quinazoline, 4-[(3-ethynyl-phenyl)amino]-6-{ [4-(5,5-dimethyl-2-oxo-morpholin-4-yl)-1-oxo-2-buten-1-y1]amino}-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{2-[4;(2-oxo-morpholin-4-yl)-piperidin-1-yl]-ethoxy}-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(trans-4-amino-cyclohexan-l-yloxy)-7-methoxy-3o quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(trans'74-methanesulphonylamino-cyclohexan-1-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(tetrahydropyran-3-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{ 1-[(morpholin-4-yl)carbonyl]-piperidin-4-yloxy }-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(piperidin-3-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[ 1-(2-acetylamino-ethyl)-piperidin-4-yloxy]-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(tetrahydropyran-4-yloxy)-7-ethoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{trans-4-[(morpholin-4-yl)carbonylamino]-cyclohexan-l-1o yloxy}-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{ 1-[(piperidin-1-yl)carbonyl]-piperidin-4-yloxy}-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(cis-4- {N-[(morpholin-4-yl)carbonyl]-N-methyl-amino}-cyclohexan-1-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(trans-4-ethansulphonylamino-cyclohexan-l-yloxy)-i 5 7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amin'o]-6-(1-methanesulphonyl-piperidin-4-yloxy)-7-(2-methoxy-ethoxy)-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[ 1-(2-methoxy-acetyl)-piperidin-4-yloxy]-7-(2-methoxy-ethoxy)-quinazoline, 4-[(3-ethynyl-phenyl)amino]-6-(tetrahydropyran-4-yloxy]-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-20 phenyl)amino]-6-(cis-4-{N-[(piperidin-1-yl)carbonyl]-N-methyl-amino}-cyclohexan-1-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6- { cis-4-[(morpholin-4-yl)carbonylamino]-cyclohexan-l--YloxY}-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-PhenY1)amino]-6-{1-[2 (2-oxopyrrolidin-1-yl)ethyl]-piperidin-4-yloxy}-7-methoxy-quinazoline, 4-25 [(3-ethynyl-phenyl)amino]-6-(1-acetyl-piperidin-4-yloxy)-7-methoxy-quinazoline, 4-[(3-ethynyl-phenyl)amino]-6-(1-methyl-piperidin-4-yloxy)-7-methoxy-quinazoline, 4-[(3-ethynyl-phenyl)amino]-6-(1-methanesulphonyl-piperidin-4-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4 fluoro-phenyl)amino]-6-(1-methyl-piperidin-4-yloxy)-7(2-methoxy-ethoxy)-3o quinazoline, 4-[(3-ethynyl-phenyl)amino]-6-{ 1-[(morpholin-4-yl)carbonyl]-piperidin-4-yloxy}-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)-amino]-6-{ 1-[(N-methyl-N-2-methoxyethyl-amino)carbonyl]-piperidin-4-yloxy}-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-ethyl-piperidin-4-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[cis-4-(N-methanesulphonyl-N-methyl-amino)-cyclohexan-1-yloxy]-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[cis-4-(N-acetyl-N-methyl-amino)-cyclohexan-l-yloxy]-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(trans-4-methylamino-cyclohexan-l-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[trans-4-(N-methanesulphonyl-N-methyl-amino)-cyclohexan-l-yloxy]-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(trans-4-dimethylamino-cyclohexan-1-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(trans-4- {N-[(morpholin-4-yl)carbonyl]-N-methyl-amino } -cyclohexan-1-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro- 4-fluoro-phenyl)amino]-6-[2-(2,2-dimethyl-6-oxo-morpholin-4-yl)-ethoxy]-7-[(S)-(tetrahydrofuran-2-yl)methoxy]-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-methanesulphonyl-piperidin-4-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-cyano-piperidin-4-yloxy)-7-methoxy-quinazoline, and 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{ 1-[(2-methoxyethyl)carbonyl]-piperidin-4-yloxy}-7-methoxy-quinazoline, optionally in the form of the racemates, enantiomers or diaitereomers thereof, optionally in the form of the pharmacologically acceptableacid addition salts thereof, the solvates and/or hydrates thereof.

By acid addition salts, salts with pharmacologically acceptable acids which the compounds may possibly be capable of forming are meant, for example, salts selected from among the hydrochloride, hydrobromide, hydriodide, hydrosulphate, hydrophosphate, hydromethanesulphonate, hydronitrate, hydromaleate, hydroacetate, hydrobenzoate, hydrocitrate, liydrofumarate, hydrotartrate, hydrooxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulphonate, preferably hydrochloride, hydrobromide; hydrosulphate, hydrophosphate, hydrofumarate and hydromethanesulphonate.

Examples of antiallergics are: disodium cromoglycate, nedocromil.
Examples of derivatives of the ergot alkaloids are: dihydroergotamine, ergotamine.

For inhalation it is possible to use pharmaceutical compositions, pharmaceutical formulations and mixtures including the above-mentioned active substances, as well as the salts, esters and combinations of these active substances, salts and esters.

List of reference numerals 1 nebuliser 27 retaining region 2 fluid 28 immersion tube 3 container 29 retaining portion 4 fluid chamber 30 closure 5 pressure generator 31 valve region 6 holder 32 valve member 7 drive spring 33 valve seat 8 blocking element 34 bead 9 conveying tube 35 connecting!portion 10 non-return valve 36 projection 11 pressure chamber 37 recess 12 expulsion nozzle 38 cylindrical portion 13 mouthpiece 39 spacer element 14 aerosol 40 connecting member 15 air inlet opening 41 connecting region 16 upper housing part 17 inner part 17a upper part of the inner part 17b lower part of the inner part 18 housing part (lower part) 19 retaining element 20 spring (in the lower housing part) 21 piercing element 22 end (of the conveying tube) 23 inner tube 24 outer tube 25 conveying channel 26 annular space

Claims

Claims:

1. Nebuliser (1) for a fluid (2), having a conveying tube (9) for conveying the fluid (2), wherein in particular the conveying tube (9) is constructed as a thick-walled capillary, characterised in that the conveying tube (9) is of double-walled construction.

2. Nebuliser according to claim 1, characterised in that the conveying tube (9) comprises an inner tube (23) and/or an outer tube (24).

3. Nebuliser according to claim 2, characterised in that between the inner tube (23) and the outer tube (24) there is formed an in particular hollow annular space (26) which is preferably sealed off in a gastight manner.

4. Nebuliser according to claim 2 or 3, characterised in that the inner tube (23) and the outer tube (24) extend concentrically with respect to one another.

5. Nebuliser according to one of claims 2 to 4, characterised in that the inner tube (23) is connected, particularly welded and/or glued, to the outer tube (24) by means of a radially widening connecting portion (35), a spacer element (39) and/or a valve member or connecting member (40).

6. Nebuliser according to claim 5, characterised in that the connecting portion (35) is formed, preferably moulded, on one end of the inner tube (23).

7. Nebuliser according to claim 5 or 6, characterised in that the connecting portion (35) has an outer diameter which at least substantially corresponds to the inner diameter of the outer tube (24).

8. Nebuliser according to one of claims 5 to 7, characterised in that the connecting portion (35) terminates flush with the end of the outer tube (24) or set back therefrom.

9. Nebuliser according to one of claims 5 to 8, characterised in that the connecting portion (35) has a conical region which forms in particular a valve seat (33).

10. Nebuliser according to one of claims 5 to 9, characterised in that the length of the connecting portion (35) is less than 20%, in particular less than 10%, of the overall length of the conveying tube (9).

11. Nebuliser according to one of claims 5 to 10, characterised in that the spacer element (39) and/or valve member or connecting member (40) is or are formed as components which are produced separately from the inner tube (23) .
and outer tube (24), particularly by deep drawing.

12. Nebuliser according to one of claims 5 to 11, characterised in that the valve member or connecting member (40) is mounted at the end of the conveying tube (9) or inner tube (23) and/or outer tube (24).

13. Nebuliser according to one of claims 5 to 12, characterised in that the valve member or connecting member (40) comprises or forms a valve region (31) having an external diameter which corresponds at least substantially to the external diameter of the outer tube (24) or conveying tube (9).

14. Nebuliser according to one of claims 5 to 13, characterised in that the valve member or connecting member (40) comprises a conical region which forms in particular a valve seat (33)

15. Nebuliser according to one of claims 5 to 14, characterised in that the length of the valve member or connecting member (40) is less than 20%, in particular less than 10% of the total length of the conveying tube (9).

16. Nebuliser according to one of claims 5 to 15, characterised in that the spacer element (39) is of sleeve-shaped construction.

17. Nebuliser according to one of claims 5 to 16, characterised in that the length of the space element (39) is less than 20%, more particularly less than 10%, of the total length of the conveying tube (9).

18. Nebuliser according to one of claims 5 to 17, characterised in that the wall thickness of the spacer element (39) amounts at least approximately to 50% of the difference between the inner diameter of the outer tube (24) and the outer diameter of the inner tube (23).

19. Nebuliser according to one of the preceding claims, characterised in that the conveying tube (9) is made up of several parts, particularly by welding and/or adhesive bonding.

20. Nebuliser according to one of the preceding claims, characterised in that the conveying tube (9) or some or all of the parts of the 'conveying tube (9) consist essentially or totally of metal, preferably stainless steel, particularly of austinitic chrome nickel steel.

21. Nebuliser according to one of the preceding claims, characterised in that the conveying tube (9) comprises a valve (10) particularly, at one end (22).

22. Nebuliser according to claims 2 and 21, characterised in that the valve (10) is formed or arranged in the outer tube (24).

23. Nebuliser according to claims 21 or 22, characterised in that the valve (10) has a valve seat (33) which is formed by the conveying tube (9) or a valve member or connecting member (40) connected thereto.

24. Nebuliser according to one of claims 21 to 23, characterised in that the conveying tube (9) comprises a separately produced valve member or connecting member (40) firmly connected to the conveying tube (9), which forms in particular a receiving chamber or valve chamber (31) for a valve member (32) of the valve (10

25. Nebuliser according to one of the preceding claims, characterised in that the conveying tube (9) has an at least substantially smooth or cylindrical outer wall (24) and/or an outer diameter which is at least substantially constant over its length.

26. Nebuliser according to one of the preceding claims, characterised in that the conveying tube (9) comprises on the outside a radial projection (36), particularly a flange-like crimp edge, and/or a radial indentation or recess (34, 37), particularly an annular groove, a depression or a bead.

27. Nebuliser according to one of the preceding claims, characterised in that the conveying tube (9) has an outer diameter of 1- 2 mm.

28. Nebuliser according to one of the preceding claims, characterised in that the length of the conveying tube (9) is at least 50 mm and/or 50 times the inner diameter of the conveying tube (9).

29. Nebuliser according to one of the preceding claims, characterised in that the conveying tube (9) has an inner diameter of 0.1 - 0.6 mm.

30. Nebuliser according to one of the preceding claims, characterised in that the conveying tube (9) has an outer diameter which is at least twice or three times as large as the inner diameter.

31. Nebuliser according to one of the preceding claims, characterised in that the conveying tube (9) has a wall thickness of at least 0.3 mm, in particular substantially 0.5 mm or more.

32. Nebuliser according to one of the preceding claims, characterised in that the nebuliser (1) is constructed so that the conveying tube (9) performs a preferably stroke-like movement during the removal of fluid, conveying of fluid pressure generation and/or atomisation.

33. Nebuliser according to one of the preceding claims, characterised in that the nebuliser (1) has a preferably insertable container (3) with a fluid chamber (4) containing the fluid (2), which is opened in particular by the attachment or insertion of the conveying tube (9) for taking fluid (2) from the container (3).

34. Nebuliser according to one of the preceding claims, characterised in that the nebuliser (1) is constructed as an inhaler, particularly for medicinal aerosol treatment or for cosmetic purposes, particularly as a perfume atomiser.

35. Method of producing a thick-walled capillary, in particular as a conveying tube (9) for a nebuliser (1) according to one of the preceding claims, the capillary being of double-walled construction consisting of several parts and/or an inner tube (23) being installed in an outer tube (24) to form the capillary.

36. Method according to claim 35, characterised in that ar!
between the inner tube (23) and the outer tube (24) is sealed off in gastight manner.

37. Method according to claim 35 or 36, characterised in that the parts are welded radially and/or axially.